Triethylamine → [5-(4-bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid 1-(3-trifluoromethyl-phenyl)-ethyl ester

HRID 631915Notes

Reaction equation

HRID 631915 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[N:11][N:10]([CH3:13])[C:9]=2C(O)=O)=[CH:4][CH:3]=1.C([N:19]([CH2:22]C)CC)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:31])=CC=1.[F:41][C:42]([F:53])([F:52])[C:43]1[CH:44]=[C:45]([CH:49]([OH:51])[CH3:50])[CH:46]=[CH:47][CH:48]=1>C1(C)C=CC=CC=1>[F:41][C:42]([F:52])([F:53])[C:43]1[CH:44]=[C:45]([CH:49]([O:51][C:22](=[O:31])[NH:19][C:9]2[N:10]([CH3:13])[N:11]=[N:12][C:8]=2[C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=2)[CH3:50])[CH:46]=[CH:47][CH:48]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1362961-(3-(Trifluoromethyl)phenyl)ethanolHCID 199401P,P-Diphenylphosphinic azideHCID 712662515-(4-Bromophenyl)-3-methyl-3H-[1,2,3]triazole-4-carboxylic acid

Product 1

HCID 118062436[5-(4-bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid 1-(3-trifluoromethyl-phenyl)-ethyl esterYield 81.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

5-(4-Bromophenyl)-3-methyl-3H-[1,2,3]triazole-4-carboxylic acid (from step 4a in Example 1, 517 mg, 1.83 mmol) was suspended in 10 mL of toluene. Triethylamine (0.27 mL) was added followed by DPPA (530 mg, 1.92 mmol) in toluene (2 mL). The mixture was stirred for 10 minutes. 3-Trifluoromethylphenylethanol (383 mg, 2.02 mmol) in toluene (2 mL) was added. The mixture was stirred at 85° C. for 3 hrs. The mixture was extracted with ethyl acetate and water. The organic layer was washed with brine and dried. Solvents were evaporated and the residue was purified by ISCO flash column chromatography (0% to 50% ethyl acetate in hexanes, 40 g silica gel) to give [5-(4-bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid 1-(3-trifluoromethyl-phenyl)-ethyl ester as an amorphous fluffy white powder (700 mg, 81.4% yield). LC/MS calcd for C19H16BrF3N4O2 (m/e) 468.0, obsd 468.9 (M+H); 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.35-1.70 (br, 3H), 3.85 (s, 3H), 5.85 (br, 1H), 7.30-7.90 (m, 8H), 10.01 (br s, 1H).

Workup

  1. stirringThe mixture was stirred at 85° C. for 3 hrs
  2. extractionThe mixture was extracted with ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. customdried
  5. customSolvents were evaporated
  6. customthe residue was purified by ISCO flash column chromatography (0% to 50% ethyl acetate in hexanes, 40 g silica gel)

Sources & evidence

ORD record
ord-ac151bc6a37f4a0397ed928a7c1ea146
Source dataset
uspto-grants-2016_04
Patent number
US09321738B2

Reaction notes

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